Ionic liquid catalyzed Ritter reaction/Pd-catalyzed directed Ortho-arylation; facile access to diverse libraries of biaryl-amides from Aryl-nitriles

Abstract

Diverse libraries of biaryl-amides bearing N-t-butyl and N-adamantyl groups were synthesized in two steps by the Ritter reaction of aryl-nitriles, using tBuOH and AdaOH as carbocation precursors, and employing [BMIM(SO3H)][OTf] (neat or with [BMIM][PF6] as co-solvent) or tetramethyl guanidinium-ILs [TMG][X] (X = CF3COO, EtOSO3) as dual catalyst/solvent, followed by a Pd-catalyzed directed regioselective ortho[sbnd]C[sbnd]H arylation of the Ritter amides with Ar-X (X = I, Cl). The feasibility to perform the two-steps in sequence is also demonstrated, and potential for recycling/reuse of the ILs is also shown. Preference for [Pd] coordination to the amide carbonyl versus amide nitrogen is borne out by DFT computations.